Osteoporosis is a major health problem afflicting millions of people worldwide. It is most prevalent in postmenopausal women, but also occurs in a significant portion of men over the age of 50. In patients on glucocorticoids, and those undergoing hormone ablation therapy for either prostate or breast cancer, bone loss and osteoporosis are especially significant. In osteoporosis patients, the decrease of bone mineral density (BMD) and bone mass content (BMC) result in increased bone fragility and risk of bone fracture. Osteoporosis may significantly affect life expectancy and quality of life.
Estrogen replacement therapy was the main approach for a long time in postmenopausal women for preventing osteoporosis until it was discovered to be associated with an increased incidence of cancer. See e.g., Prentice et al., Am. J. Epidemiol., 170(1):12-23 (2009). Bisphosphonates were first developed in mid 1990s and have become the main pharmaceutical measures for osteoporosis. However, oral bisphosphonates are poorly absorbed and are often associated with esophageal inflammation. Recently, RANKL-targeting antibodies such as denosumab have shown some promise as effective agents in reducing bone resorption. See e.g., McClung et al., N. Engl. J. Med., 354(8):821-31 (2006).